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Myeloid derived suppressor cells

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https://www.readbyqxmd.com/read/28934717/expression-of-c-ebp%C3%AE-in-myeloid-progenitors-during-sepsis-promotes-immunosuppression
#1
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs...
September 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28932631/tadalafil-has-biologic-activity-in-human-melanoma-results-of-a-pilot-trial-with-tadalafil-in-patients-with-metastatic-melanoma-tame
#2
Jessica C Hassel, Huanhuan Jiang, Carolin Bender, Julia Winkler, Alexandra Sevko, Ivan Shevchenko, Niels Halama, Antonia Dimitrakopoulou-Strauss, Walter E Haefeli, Dirk Jäger, Alexander Enk, Jochen Utikal, Viktor Umansky
Myeloid-derived suppressor cells (MDSCs) are known to play a critical role in the suppression of T cell antitumor responses. Our preclinical data showed that the phosphodiesterase (PDE)-5 inhibitor sildenafil impaired MDSC functions, enhanced intratumoral T cell activity and prolonged survival of melanoma-bearing mice. In this study, we evaluated biologic effects, safety and efficacy of palliative treatment with the PDE-5 inhibitor tadalafil in metastatic melanoma patients. We conducted an open-label, dose de-escalation trial with tadalafil in pretreated metastatic melanoma patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#3
REVIEW
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928446/tumour-derived-pgd2-and-nkp30-b7h6-engagement-drives-an-immunosuppressive-ilc2-mdsc-axis
#4
Sara Trabanelli, Mathieu F Chevalier, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Bérengère Salomé, Mariangela Lecciso, Valentina Salvestrini, Grégory Verdeil, Julien Racle, Cristina Papayannidis, Hideaki Morita, Irene Pizzitola, Camille Grandclément, Perrine Bohner, Elena Bruni, Mukul Girotra, Rani Pallavi, Paolo Falvo, Elisabeth Oppliger Leibundgut, Gabriela M Baerlocher, Carmelo Carlo-Stella, Daniela Taurino, Armando Santoro, Orietta Spinelli, Alessandro Rambaldi, Emanuela Giarin, Giuseppe Basso, Cristina Tresoldi, Fabio Ciceri, David Gfeller, Cezmi A Akdis, Luca Mazzarella, Saverio Minucci, Pier Giuseppe Pelicci, Emanuela Marcenaro, Andrew N J McKenzie, Dominique Vanhecke, George Coukos, Domenico Mavilio, Antonio Curti, Laurent Derré, Camilla Jandus
Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28920004/targeting-myeloid-derived-suppressor-cells-with-all-trans-retinoic-acid-is-highly-time-dependent-in-therapeutic-tumor-vaccination
#5
Annkristin Heine, Chrystel Flores, Heidrun Gevensleben, Linda Diehl, Mathias Heikenwalder, Marc Ringelhan, Klaus-Peter Janssen, Ulrich Nitsche, Natalio Garbi, Peter Brossart, Percy A Knolle, Christian Kurts, Bastian Höchst
Tumor immune escape is a critical problem which frequently accounts for the failure of therapeutic tumor vaccines. Among the most potent suppressors of tumor immunity are myeloid derived suppressor cells (MDSCs). MDSCs can be targeted by all-trans-retinoic-acid (atRA), which reduced their numbers and increased response rates in several vaccination studies. However, not much is known about the optimal administration interval between atRA and the vaccine as well as about its mode of action. Here we demonstrate in 2 different murine tumor models that mice unresponsive to a therapeutic vaccine harbored higher MDSC numbers than did responders...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28920002/ep4-antagonism-by-e7046-diminishes-myeloid-immunosuppression-and-synergizes-with-treg-reducing-il-2-diphtheria-toxin-fusion-protein-in-restoring-anti-tumor-immunity
#6
Diana I Albu, Zichun Wang, Kuan-Chun Huang, Jiayi Wu, Natalie Twine, Sarah Leacu, Christy Ingersoll, Lana Parent, Winnie Lee, Diana Liu, Renee Wright-Michaud, Namita Kumar, Galina Kuznetsov, Qian Chen, Wanjun Zheng, Kenichi Nomoto, Mary Woodall-Jappe, Xingfeng Bao
Reprogramming of immunosuppressive tumor microenvironment (TME) by targeting alternatively activated tumor associated macrophages (M2TAM), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), represents a promising strategy for developing novel cancer immunotherapy. Prostaglandin E2 (PGE2), an arachidonic acid pathway metabolite and mediator of chronic inflammation, has emerged as a powerful immunosuppressor in the TME through engagement with one or more of its 4 receptors (EP1-EP4). We have developed E7046, an orally bioavailable EP4-specific antagonist and show here that E7046 has specific and potent inhibitory activity on PGE2-mediated pro-tumor myeloid cell differentiation and activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28912395/-cytotoxic-agents-and-immune-checkpoint-inhibitors
#7
Akihito Kawazoe, Kohei Shitara
It has been reported that favorable influences of cytotoxic agents to anti-tumor immune response included immunogenic cell death and suppression of regulatory T cell and myeloid-derived suppressor cell. Some clinical trials showed that the addition of immune checkpoint inhibitor to standard chemotherapy improved efficacy in patients with non-small-cell lung cancer or malignant melanoma in first-line settings. Phase III trials of the combination of immune checkpoint inhibitor and chemotherapy in several malignancies are ongoing...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912136/tumor-resection-boosts-therapeutic-efficacy-of-encapsulated-stem-cells-expressing-a-highly-secretable-variant-of-interferon-%C3%AE-in-glioblastomas
#8
Sung Hugh Choi, Daniel W Stuckey, Sara Pignatta, Clemens Reinshagen, Jasneet K Khalsa, Nicolaas C Roozendaal, Jordi Martinez-Quintanilla, Kaoru Tamura, Erhan Keles, Khalid Shah
PURPOSE: Despite tumor resection being the frontline clinical care for glioblastoma (GBM) patients, nearly all preclinical immune therapy models intends to treat established GBM tumor. Characterizing cytoreductive surgery-induced immune-response combined with the administration of immune cytokines has the potential of offering a new treatment paradigm of immune therapy for GBMs.  Experimental design: We developed syngeneic orthotopic mouse GBM models of tumor-resection and characterized the immune response of intact and resected tumors...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28910953/-the-expression-and-association-of-cd14-hla-dr-low-myeloid-derived-suppressor-cell-like-cells-and-interleukin-1%C3%AE-in-ovarian-cancer
#9
H Y Wang, R Zhao, H Ren, M J Zou, J Zhang, Y Zhang
Objective: To analyze the percentage of CD14(+) HLA-DR(Low/-) myeloid-derived suppressor cell-like cell subtypes(MDSCs) and interleukin-1β(IL-1β) concentration in peripheral blood and ascites of ovarian cancer patients, and to explore their association with clinicopathological characteristics. Methods: Blood samples of 31 patients and ascites of 5 patients in Qilu Hospital of Shandong University from January 2016 to December 2016 were collected. Blood samples of 20 healthy volunteers with matched age were collected as control...
September 12, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28904063/anti-jagged-immunotherapy-inhibits-mdscs-and-overcomes-tumor-induced-tolerance
#10
Rosa A Sierra, Jimena Trillo-Tinoco, Eslam Mohamed, Lolie Yu, Bhagelu R Achyut, Ali Arbab, Jennifer W Bradford, Barbara A Osborne, Lucio Miele, Paulo C Rodriguez
Myeloid-derived suppressor cells (MDSCs) are a major obstacle to promising forms of cancer immunotherapy, but tools to broadly limit their immunoregulatory effects remain lacking. In this study, we assessed the therapeutic effect of the humanized anti-Jagged1/2 blocking antibody CTX014 on MDSC-mediated T cell suppression in tumor-bearing mice. CTX014 decreased tumor growth, impacted the accumulation and tolerogenic activity of MDSCs in tumors, and inhibited the expression of immunosuppressive factors arginase I and iNOS...
September 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28903971/extracellular-s100a9-protein-in-bone-marrow-supports-multiple-myeloma-survival-by-stimulating-angiogenesis-and-cytokine-secretion
#11
Kim De Veirman, Nathan De Beule, Ken Maes, Eline Menu, Elke De Bruyne, Hendrik De Raeve, Karel Fostier, Jerome Moreaux, Alboukadel Kassambara, Dirk Hose, Roy Heusschen, Helena Eriksson, Karin Vanderkerken, Els Van Valckenborgh
Dysregulated expression of S100 protein family members is associated with cancer proliferation, invasion, angiogenesis, and inflammation. S100A9 induces myeloid-derived suppressor cell (MDSC) accumulation and activity. MDSCs, immunosuppressive cells that contribute to tumor immune escape, are the main producers of S100A9. In this study, we evaluated the role of extracellular S100A9 and the therapeutic relevance of S100A9 inhibition in multiple myeloma (MM), using the immunocompetent murine 5T33MM model. We demonstrated the presence of S100A9 and its receptor TLR4 in both monocytic and granulocytic MDSCs in human and mouse samples...
September 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28903332/myeloid-derived-suppressor-cell-and-macrophage-exert-distinct-angiogenic-and-immunosuppressive-effects-in-breast-cancer
#12
Zhaoxu Fang, Chengwen Wen, Xiaolan Chen, Rongping Yin, Chenglin Zhang, Xiaohua Wang, Yuhui Huang
The immunosuppressive tumor microenvironment is a key obstacle to hinder a cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) have been considered as a major player in immunosuppression. In this study, we find that tumor-infiltrating MDSCs (tiMDSCs) are less immunosuppressive than tumor-associated macrophages (TAMs) in multiple murine orthotopic breast tumor models. Compared to TAMs, tiMDSCs produce higher levels of pro-inflammatory factors and lower levels of anti-inflammatory factors. Furthermore, tiMDSCs are preferentially located in hypoxic areas and are more pro-angiogenic than TAMs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900509/biodegradable-hollow-mesoporous-silica-nanoparticles-for-regulating-tumor-microenvironment-and-enhancing-antitumor-efficiency
#13
Miao Kong, Jiamin Tang, Qi Qiao, Tingting Wu, Yan Qi, Songwei Tan, Xueqin Gao, Zhiping Zhang
There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β...
2017: Theranostics
https://www.readbyqxmd.com/read/28898532/immunological-efficacy-of-herbal-medicines-in-prostate-cancer-patients-treated-by-personalized-peptide-vaccine
#14
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HMs or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for the eight-time subcutaneous injection of PPV according to the patient's human leukocyte antigen type and levels of antigen-specific immunoglobulin G (IgG) titer before PPV treatment...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28894087/hypoxia-inducible-factor-hif-1-promotes-myeloid-derived-suppressor-cells-accumulation-through-entpd2-cd39l1-in-hepatocellular-carcinoma
#15
David Kung-Chun Chiu, Aki Pui-Wah Tse, Iris Ming-Jing Xu, Jane Di Cui, Robin Kit-Ho Lai, Lynna Lan Li, Hui-Yu Koh, Felice Ho-Ching Tsang, Larry Lai Wei, Chun-Ming Wong, Irene Oi-Lin Ng, Carmen Chak-Lui Wong
Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28890718/transmembrane-tumor-necrosis-factor-controls-myeloid-derived-suppressor-cell-activity-via-tnf-receptor-2-and-protects-from-excessive-inflammation-during-bcg-induced-pleurisy
#16
Leslie Chavez-Galan, Dominique Vesin, Husnu Uysal, Guillaume Blaser, Mahdia Benkhoucha, Bernhard Ryffel, Valérie F J Quesniaux, Irene Garcia
Pleural tuberculosis (TB) is a form of extra-pulmonary TB observed in patients infected with Mycobacterium tuberculosis. Accumulation of myeloid-derived suppressor cells (MDSC) has been observed in animal models of TB and in human patients but their role remains to be fully elucidated. In this study, we analyzed the role of transmembrane TNF (tmTNF) in the accumulation and function of MDSC in the pleural cavity during an acute mycobacterial infection. Mycobacterium bovis BCG-induced pleurisy was resolved in mice expressing tmTNF, but lethal in the absence of tumor necrosis factor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28888039/role-of-aldh1-in-the-prognosis-of-esophageal-cancer-and-its-relationship-with-tumor-microenvironment
#17
Miao-Fen Chen, Ping-Tsung Chen, Ming-Shian Lu, Wen-Cheng Chen
Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate and shorter survival time...
September 9, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#18
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28881585/c-ebp-%C3%AE-positively-regulates-mdsc-expansion-and-endothelial-vegfr2-expression-in-tumor-development
#19
Yongfen Min, Jingdong Li, Peng Qu, P Charles Lin
Vascular endothelial cells and Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) are two important components that constitute the tumor microenvironment. Targeting these cells offers the potential to halt tumor growth. In this study, we report a common mediator in C/EBP-δ that regulates both components and aids in tumor development. C/EBP-δ is elevated in tumor derived MDSCs. Interestingly, genetic deletion of C/EBP-δ in mice significantly impaired MDSC expansion in response to tumor progression, but it had no effect on Gr-1+CD11b+ cell production in normal development...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877631/pm01183-inhibits-myeloid-derived-suppressor-cells-in-vitro-and-in-vivo
#20
Hiromasa Kuroda, Seiji Mabuchi, Katsumi Kozasa, Eriko Yokoi, Yuri Matsumoto, Naoko Komura, Mahiru Kawano, Kae Hashimoto, Kenjiro Sawada, Tadashi Kimura
AIM: To evaluate the ability of PM01183 to eliminate myeloid-derived suppressor cells (MDSCs). MATERIALS & METHODS: The effect of PM01183 on MDSCs, NK cells and CD8(+) T cells was examined in vitro and in vivo. The mechanism by which PM01183 depletes MDSCs was also investigated. RESULTS: PM01183 reduced the number of MDSCs by inducing apoptosis and attenuated the MDSC-mediated suppression of CD8(+) T cells by inhibiting arginase-1 production, whereas no significant effect on CD8(+) T or NK cells was noted...
September 2017: Immunotherapy
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